Biodegradable targetable microparticle delivery system

Abstract

Copolymers designed for use as particulate carriers containing functionalizable amino acid subunits for coupling with targeting ligand are described. The copolymers are polyesters composed of α-hydroxy acid subunits such as D,L-lactide and α-amino acid subunits such as serine or in the preferred embodiment, terpolymers of D,L-lactide and glycolide and α-amino acid subunits such as serine. Stable vaccine preparations useful as delayed release formulations containing antigen(s) or antigen(s) and co-adjuvants encapsulated within or physically mixed with polymeric microparticles are described. The particulate carriers are useful for delivering agents to the immune system of a subject by mucosal or parenteral routes to produce immune responses, including antibody responses.

What we claim is:  
     
       1. A process for making a biodegradable, biocompatible polymer of the formula:                    
       wherein:  
       R 1 , R 2  and R 5  are selected independently and are selected from H, linear or branched alkyl groups;  
       R 3  and R 4  are H;  
       R 6  is selected from H, an amine protecting group, a spacer molecule or a biologically active species;  
       X is selected from an O or S group; and  
       X and y are integers such that at least about 95% of the polymer is comprised of α-hydroxy acid residues, which comprises:  
       forming a mixture of monomers comprising at least one α-hydroxy acid and at least one α-amino acid having an amine protecting group with an organic solvent solution of an esterification catalyst under inert atmospheric conditions;  
       copolymerizing said monomers; and  
       isolating the resultant polymer.  
     
     
       2. The process of claim  1 , wherein the polymer formed is deprotected by solid phase catalytic reduction or acid catalysis. 
     
     
       3. The process of claim  2 , wherein said deprotection is by acid catalysis in the presence of hydrogen bromide in acetic acid solution. 
     
     
       4. The process of claim  1 , wherein said catalyst is stannous 2-ethylhexanoate. 
     
     
       5. The process of claim  1 , wherein said polymerization is carried out at a temperature of about 120° C. for about 28 hours. 
     
     
       6. The process of claim  1 , wherein said organic solvent is anhydrous chloroform. 
     
     
       7. The process of claim  1 , wherein said process further comprises forming the polymer into a film. 
     
     
       8. The process of claim  1 , wherein said process further comprises forming the polymer into microparticles.